Abstract
1. Guanylate cyclase activity was determined in homogenates of guinea-pig islets of Langerhans by measurement of the conversion of [α-32P]GTP into cyclic [32P]GMP, the reaction products being separated on columns of neutral alumina. 2. The pH optimum of the enzyme was 7.3; it showed a requirement for bivalent cations, the effectiveness of the cations tested being Mn2+»Ca2+>Mg2+. 3. About 70% of enzyme activity was sedimented by centrifugation at 105000g for 60min; activity was increased 2.3-fold by treatment of homogenates with 0.1% Triton X-100. 4. Guanylate cyclase activity of homogenates was increased by acetylcholine, secretin or pancreozymin, but was inhibited by adrenaline, noradrenaline or ATP. Insulin, glucagon, prostaglandins E1 or E2, glucose, F−, diazoxide or glibenclamide were ineffective. 5. Determination of cyclic GMP amounts in islets by radioimmunoassay showed a basal concentration of 2.0pmol/mg of protein, which was increased by incubation of the islets in the presence of acetylcholine or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, but was unaffected by glucose. 6. Dibutyryl cyclic GMP had significant stimulatory effects on rates of insulin biosynthesis in isolated rat islets of Langerhans. 7. These results suggest a possible role for cyclic GMP in the regulation of insulin biosynthesis and secretion.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bensinger R. E., Fletcher R. T., Chader G. J. Guanylate cyclase: inhibition by light in retinal photoreceptors. Science. 1974 Jan 11;183(4120):86–87. doi: 10.1126/science.183.4120.86. [DOI] [PubMed] [Google Scholar]
- Clark J. L., Steiner D. F. Insulin biosynthesis in the rat: demonstration of two proinsulins. Proc Natl Acad Sci U S A. 1969 Jan;62(1):278–285. doi: 10.1073/pnas.62.1.278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
- Davis B., Lazarus N. R. Insulin release from mouse islets. Effect of glucose and hormones on adenylate cyclase. Biochem J. 1972 Sep;129(2):373–379. doi: 10.1042/bj1290373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- George W. J., Polson J. B., O'Toole A. G., Goldberg N. D. Elevation of guanosine 3',5'-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Natl Acad Sci U S A. 1970 Jun;66(2):398–403. doi: 10.1073/pnas.66.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goridis C., Virmaux N., Urban P. F., Mandel P. Guanyl cyclase in a mammalian photoreceptor. FEBS Lett. 1973 Mar 1;30(2):163–166. doi: 10.1016/0014-5793(73)80642-8. [DOI] [PubMed] [Google Scholar]
- Green I. C., Howell S. L., Montague W., Taylor K. W. Regulation of insulin release from isolated islets of Langerhans of the rat in pregnancy. The role of adenosine 3':5'-cyclic monophosphate. Biochem J. 1973 Jun;134(2):481–487. doi: 10.1042/bj1340481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hardman J. G., Sutherland E. W. Guanyl cyclase, an enzyme catalyzing the formation of guanosine 3',5'-monophosphate from guanosine trihosphate. J Biol Chem. 1969 Dec 10;244(23):6363–6370. [PubMed] [Google Scholar]
- Howell S. L., Green I. C., Montague W. A possible role of adenylate cyclase in the long-tern dietary regulation of insulin secretion from rat islets of Langerhans. Biochem J. 1973 Oct;136(2):343–349. doi: 10.1042/bj1360343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howell S. L., Montague W. Adenylate cyclase activity in isolated rat islets of Langerhans. Effects of agents which alter rates of insulin secretion. Biochim Biophys Acta. 1973 Aug 17;320(1):44–52. doi: 10.1016/0304-4165(73)90163-3. [DOI] [PubMed] [Google Scholar]
- Howell S. L., Taylor K. W. Effects of glucose concentration on incorporation of [3H]leucine into insulin using isolated mammalian islets of Langerhans. Biochim Biophys Acta. 1966 Dec 28;130(2):519–521. doi: 10.1016/0304-4165(66)90250-9. [DOI] [PubMed] [Google Scholar]
- Howell S. L., Whitfield M. Cytochemical localization of adenyl cyclase activity in rat islets of Langerhans. J Histochem Cytochem. 1972 Nov;20(11):873–879. doi: 10.1177/20.11.873. [DOI] [PubMed] [Google Scholar]
- Ishikawa E., Ishikawa S., Davis J. W., Sutherland E. W. Determination of guanosine 3',5'-monophosphate in tissues and of guanyl cyclase in rat intestine. J Biol Chem. 1969 Dec 10;244(23):6371–6376. [PubMed] [Google Scholar]
- Kuo W. N., Hodgins D. S., Kuo J. F. Adenylate cyclase in islets of Langerhans. Isolation of islets and regulation of adenylate cyclase activity by various hormones and agents. J Biol Chem. 1973 Apr 25;248(8):2705–2711. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Macchia V., Varrone S. Mechanism of TSH action. Studies with dibutyryl cyclic AMP and dibutyryl cyclic GMP. FEBS Lett. 1971 Apr 2;13(6):342–344. doi: 10.1016/0014-5793(71)80256-9. [DOI] [PubMed] [Google Scholar]
- Schatz H., Maier V., Hinz M., Nierle C., Pfeiffer E. F. Stimulation of H-3-leucine incorporation into the proinsulin and insulin fraction of isolated pancreatic mouse islets in the presence of glucagon, theophylline and cyclic AMP. Diabetes. 1973 Jun;22(6):433–441. doi: 10.2337/diab.22.6.433. [DOI] [PubMed] [Google Scholar]
- Steiner A. L., Parker C. W., Kipnis D. M. Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides. J Biol Chem. 1972 Feb 25;247(4):1106–1113. [PubMed] [Google Scholar]
- Thompson W. J., Williams R. H., Little S. A. Studies on the assay and activities of guanyl and adenyl cyclase of rat liver. Arch Biochem Biophys. 1973 Nov;159(1):206–213. doi: 10.1016/0003-9861(73)90446-3. [DOI] [PubMed] [Google Scholar]
- Varrone S., Di Lauro R., Macchia V. Stimulation of polypeptide synthesis by cyclic 3'-5'-guanosine monophosphate. Arch Biochem Biophys. 1973 Aug;157(2):334–338. doi: 10.1016/0003-9861(73)90647-4. [DOI] [PubMed] [Google Scholar]
- Voyles N., Gutman R. A., Selawry H., Fink G., Penhos J. C., Recant L. Interaction of various stimulators and inhibitors on insulin secretion in vitro. Horm Res. 1973;4(2):65–73. doi: 10.1159/000178291. [DOI] [PubMed] [Google Scholar]
- White A. A., Zenser T. V. Separation of cyclic 3',5'-nucleoside monophosphates from other nucleotides on aluminum oxide columns. Application to the assay of adenyl cyclase and guanyl cyclase. Anal Biochem. 1971 Jun;41(2):372–396. doi: 10.1016/0003-2697(71)90156-4. [DOI] [PubMed] [Google Scholar]
- Yamashita K., Field J. B. Elevation of cyclic guanosine 3',5'-monophosphate levels in dog thyroid slices caused by acetylcholine and sodium fluoride. J Biol Chem. 1972 Nov 10;247(21):7062–7066. [PubMed] [Google Scholar]